Goal of Label Changes: Better Prescribing, Safer Use of Opioids

Consumers and health care professionals will soon find updated labeling for
extended-release and long-acting opioid pain relievers to help ensure their safe
and appropriate use.

In addition to requiring new labeling on these prescription medications, the
Food and Drug Administration (FDA) is also requiring manufacturers to study
certain known serious risks when these drugs are used long-term.

"The new labeling requirements and other actions are intended to help
prescribers and patients make better decisions about who benefits from the use
of these medications. They also are meant to reduce problems associated with
their use," says Douglas Throckmorton, M.D., deputy director of regulatory
programs in FDA's Center for Drug Evaluation and Research. "Altogether, the
actions we're now announcing are part of FDA's efforts to make opioids as safe
as possible for those who need them," Throckmorton adds.

He noted that the actions come after careful analysis of new safety
information, including reviews of medical literature, and consideration of input
from patients, experts and many other interested parties.

How Labeling Will Change

Opioids work by changing the way the brain perceives pain. They are available
by prescription as pills, liquids, and skin patches. Extended-release and
long-acting (ER/LA) forms pose a greater safety concern because - as their names
suggest - they produce their effects for a longer period, and many contain higher
doses compared with immediate release or opioid/non-opioid combination products.
They include, to name a few, long acting versions of opioids such as morphine,
oxycodone, and fentanyl.

Currently, labeling on these ER/LA opioids indicate they are for "the relief
of moderate to severe pain in patients requiring continuous, around-the-clock
opioid treatment for an extended period of time."

However, the updated indication for when to prescribe and take these
medicines will, when finalized, emphasize that other, less potentially
addictive, treatment options should be considered first.

FDA is requiring labeling that says the drugs are "indicated for the
management of pain severe enough to require daily, around-the-clock, long-term
opioid treatment and for which alternative treatment options are inadequate."

The "limitations of use" portion of the new labeling retains language
indicating that the drugs are not intended for use as an "as-needed" pain
reliever. Furthermore, the new labeling adds: "Because of the risks of
addiction, abuse and misuse with opioids, even at recommended doses, and because
of the greater risks of overdose and death with extended-release opioid
formulations, reserve [Tradename] for use in patients for whom alternative
treatment options (e.g., non-opioid analgesics or immediate-release opioids) are
ineffective, not tolerated, or would be otherwise inadequate to provide
sufficient management of pain."

This new labeling language emphasizes that patients in pain should be
assessed not only by their rating on a pain intensity scale, but also based on a
more thoughtful determination that their pain - however it may be defined - is
severe enough to require daily, around-the-clock, long-term opioid treatment,
and for which alternative treatment options are inadequate.

This framework better enables prescribers to make decisions based on a
patient's individual needs, given the serious risks associated with ER/LA
opioids, against a backdrop of alternatives such as immediate release (IR)
opioids and non-opioid pain relievers. It allows prescribers to make an
assessment of pain relative to a patient's ability to perform daily activities
or enjoy a reasonable quality of life.

FDA-approved labeling of these pain relievers already describes the effects
on newborns of exposure to these drugs while in the mother's womb and warns
against use by women
during pregnancy and
labor and while
nursing. The new
labeling, however, will provide more detail and will elevate the risk of
neonatal opioid withdrawal syndrome (NOWS) to the most prominent position in
labeling - a boxed warning. Symptoms of NOWS may include poor feeding, rapid
breathing, trembling, and excessive or high-pitched crying.

Postmarket Studies

Recognizing the need for more scientific data about the benefits and risks of
ER/LA opioids when used over long periods, FDA also decided to require drug
companies to conduct longer term studies and trials of ER/LA opioid pain
relievers on the market.

The companies must evaluate long-term use, with the goal of assessing a
variety of known serious risks, including misuse, abuse, addiction, overdose,
and death, as well as the risks of developing increasing sensitivity to pain.

Education to Reduce Risk

Following implementation of the safety labeling changes, certain educational
materials for patients and health care professionals will be modified to reflect
the new labeling for the ER/LA opioid pain relievers. As part of the new
labeling changes, opioid manufacturers also must revise a paper handout patients
receive with their prescription.

The ER/LA Opioid Analgesics Risk Evaluation and Mitigation Strategy (REMS)
will also be updated after the labeling changes are finalized. The ER/LA Opioid
Analgesics REMS requires manufacturers to make available continuing education
courses for health care professionals who prescribe these drugs. The courses,
from accredited sources, teach about risks and safe prescribing and safe use
practices of these medications.

"By improving information about the risks of ER/LA opioid pain relievers and
by clarifying the populations for whom the benefits outweigh the risks, we aim
to improve the safe and appropriate use of these products," says Throckmorton.

He adds: "This is not the first or last initiative, and we will continue
supporting broader efforts to solve the serious public health problems
associated with the misuse and abuse of opioids."